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Home > Scientific articles
Jun 2021

Identification of resistance determinants for a promising antileishmanial oxaborole series

Microorganisms

by Van den Kerkhof M, Leprohon P, Mabille D, Hendrickx S, Tulloch LB, Wall RJ, Wyllie S, Chatelain E, Mowbray CE, Braillard S, Ouellette M, Maes L, Caljon G. Microorganisms 2021; 9(7):1408. doi: 10.3390/microorganisms9071408

Summary: DNDI-6148 is an oxaborole under development for the treatment of visceral leishmaniasis. It is important to identify the Leishmania target(s) and additional resistance determinants of DNDI-6148 for its clinical development and possible selection of a partner drug for combination therapy. This study evaluated the likelihood of resistance emergence and found that prolonged exposure to DNDI-6148 (and back-up compound DNDI-5421) did not lead to the emergence of compound-resistant parasites. This study confirmed that these compounds do not share the efflux transporter-related resistance mechanism common to several antileishmanials. Screening of two overexpression libraries identified genes from chromosome 2 that provide a slight advantage under drug pressure, but additional studies are needed to investigate this further.

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Visceral leishmaniasis

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